Domain families genome analysis

S, Johnston C, SiUero A, Thornton J, Orengo C (2005) The CATH domain structure database and related resources Gene3D and DHS provide comprehensive domain family information for genome analysis. Nucleic Acids Res 33 D247-D251... 

Interpretation of results of these studies is still difficult. Results of two-hybrid methods become more useful if they can be coordinated with other approaches. For example, computational methods can predict interactions from genome sequences alone. 11/0 More than 45,000 interactions have been predicted among yeast proteins. Reliable identification of such motifs as DNA-binding domains and Ca2+- binding domains can complement two-hybrid analysis.11 The yeast genome is predicted to contain 162 coiled-coil sequences and at least 213 unique interactions between them.0 Examination of sequences of protein families in the Protein Data Bank (PDB) led to prediction of 8151 interactions of 664 types between protein families in yeast.P... 

Occurrence profiles involving functions, pathways, and other genomic data are used in comparative analysis in a way similar to that previously discussed for genes. For example, occurrence or abundance profiles of certain COGs (such as signal transduction histidine kinase, serine/threonine protein kinase, and phosphatase) can provide a broad overview of protein families present or absent in the genomes of interest, whereas occurrence profiles of Pfam domains found in these proteins could provide additional information on the signals sensed by the proteins. 

The putative kinase domains are not highly conserved over evolution. The N-terminal kinase domain has weak similarity to a protein kinase family, whereas the C-terminal domains shows no similarity to any known kinase. Further characterization of the N-terminal kinase domain indicates that acidic residues in two small regions are important for the kinase activity (O Brien and Tjian, 1998). Combined mutation of both regions disrupts kinase activity, and the mutant has reduced ability to rescue the ts 13 cell line, a ts hamster cell line with a mutation in TAFl. This mutant shows a defect in transcription of approximately 6% in a genome-wide analysis (O Brien and Tjian, 2000), indicating that the kinase activity of the N-terminal domain may be required for expression of a subset of genes in vivo. 

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